维甲酸类衍生物诱导K562细胞分化的活性筛选

Screening of the activity of K562 cell differentiation induced by retinoic acid derivatives

目的探讨维甲酸类衍生物对白血病细胞株K562细胞的抑制增殖和诱导分化活性,以寻找新的具有抗瘤活性的药物。方法在体外通过四甲基偶氮唑蓝(MTT)试验法检测其对细胞生长抑制的作用;瑞氏染色法观察细胞形态学改变;硝基四唑氮蓝(NBT)还原实验法分析细胞的分化指标;利用流式细胞术检测细胞表面分化抗原及细胞周期的变化情况。结果维甲酸类衍生物作用3 d后,细胞增殖抑制率最高可达到57.74%,IC50为2.82E-05;油镜下观察发现细胞形态学趋向成熟,NBT还原实验也表明维甲酸类衍生物具有诱导K562细胞株分化成熟的作用;细胞周期分析显示细胞表面分化抗原CD11b表达量增加,G0/G1期细胞增加,而S期减少。结论维甲酸类衍生物对K562细胞具有诱导分化并对其克隆生长有抑制作用,其中以2a-03、4a-01、4a-02和5a-02的作用较为突出,进一步研究开发有一定的价值。

Objective To investigate the effects of the ten novel retinoic acid derivatives on the differentiation and clonal proliferation of K562 cells to search new medicine for carcinoma. Methods MTT, cell morphological examination, nitro tetrazolium blue reduction test, flow cytometry were used to observe the alteration of proliferation, differentiation characteristics,cell cycle and the expression of the maturation specific cell surface marker CD11b. Results After 72 hours treatment with retinoic acid derivatives, they remarkably inhibited growth of K562 cells in a dosedependent manner, the maximal value of inhibition ratio and IC50 amounted to 57.74% and 2.82E-05 respectively. Cell morphous was observed to be mature in immersion objective. Nitro tetrazolium blue reduction test still indicated that the retinoic acid derivatives could induce differentiation of K562 cells. The expression of the maturation specific cell surface marker CD11b increased. The proportion of cells in GO/G1 phase increased while the cells in S phase decreased. Conclusion These retinoic acid derivatives, especially retinoid 2a-03,4a-01,4a-02 and 5a-02, may regulate the proliferation ,induce K562 cells differentiation and maturation, and is worthy of further study.